Solvent Scales ε α β α: solvent's ability to act as a hydrogen bond-donor to a solute Water 78 1.17 0.47 DMS 47 0.00 0.76 DM 37 0.00 0.76 Methanol 33 0.93 0.66 MPA 29 0.00 1.05 Acetone 21 0.08 0.43 Methylene Chloride 9 0.13 0.10 T 8 0.00 0.55 Ethyl acetate 6 0.00 0.45 Ether 4 0.00 0.47 Benzene 2 0.00 0.10 exane 2 0.00 0.00 β: solvent's ability to act as a hydrogen bond acceptor from a solute ε: Dielectric constant: correlates with solvent polarity (molecular dipoles, molecular polarizabilities hydrogen bonding capability, etc)
ydrogen Bond Strengths =C formic acid-formic acid -7.4 kcal/mol (gas phase) methanol-methanol -7.6 kcal/mol (gas phase) R 2 Phenol - dioxane -5.0 kcal/mol (CCl 4 ) SR 2 Phenol-butyl sulfide -4.2 kcal/mol (CCl 4 ) SeR 2 Phenol-butyl selenide -3.7 kcal/mol (CCl 4 ) sp 2 Phenol-Pyridine -6.5 kcal/mol (CCl 4 ) sp 3 Phenol-Triethylamine -8.4 kcal/mol (CCl 4 ) SR 2 thiocyanic acid-butyl sulfide -3.6 kcal/mol (CCl 4 )
on-covalent Interactions 1. Ion-Pairing E = q 1 q 2 /4πεε ο r Example: salt bridge in proteins 3 + Strength of the interaction depends on context: dielectric constant in denominator, therefore high polarity solvents have weak interactions between charges LDA T ε=8 q=charge (in coulombs) of ion Li MPA ε=29 - E + Li+ Me 2 P - Me 2 Me 2 β=1.05: best acceptor of -bond or M + E 2. Ion-Dipole E = µq 2 cosθ/4πεε ο r 2 weaker:falls off more rapidly with distance a + The smaller the ion, the greater the solvation/hydration energy: Li + >a + >K + >Rb + reason: more charge per unit µ=dipole moment area on smaller ion. of polar molecule
on-covalent Interactions 3. Dipole-Dipole E = µ 1 µ 2 (3cos 2 θ 1)/4πεε ο r 3 the force between two dipoles depends on their relative orientation Cl δ δ + δ δ + ydrogen Bonding: a donor-acceptor interaction whose governed primarily by electrostatic considerations: δ δ + δ Any partial negative chage can accept Dn :Ac -bond ptimal geometry is a colinear arrangement of three atoms, but geometry is not a major contributing factor to -bond strength D lone pairs are diffuse and have weak directionality Bifurcated -bonds are possible: D A A A D D
Strength of -Bonds: ydrogen Bonding Very Strong 15-40 kcal/mol Moderate 5-14 kcal/mol Weak 0-4 kcal/mol Solvent influences the strength of ydrogen Bonds: ydrogen bond exists in CCl 4, not in dioxane: or competitive solvents: D S + A S D A + S S Electronegativity: donor ability: > Cl > Br > I acceptor ability: 3 > 2 > 2 S > 3 P diffuse electron pairs of third row elements make them poor acceptors Strong hydrogen bonds occur when both partners are charged: Resonance-Assisted ydrogen Bonding - - -
ydrogen Bonding Cooperative ydrogen bonding: assisted polarization of Dn- bond, making them better donors: Secondary Interactions: primary secondary (repulsive) secondary (stabilizing) Short-Strong ydrogen Bonds: low barrier/no barrier -bonds arise when the distance between Dn and A is short (2.4-2.5Å) proton sponges: donor and acceptor pushed together Me Me three center four electron bond pka=12.1 pka=16.1
π Effects Cation-π Interaction: interaction between the face of a simple pi system (with negative electrostatic potential and a cation: ΔG (kcal/mol) Li + 38 a + 27 K + 19 Rb 16 Csp 2 is more electronegative than! 2 K + -18 kcal/mol 2 C 6 6-19 kcal/mol binding of a + 2 C Also: 27.1 22.0 26.9 31.8 15.7 kcal/mol In Proteins: 3 +
Polar-π Interactions 1.9 kcal/mol 1.4 kcal/mol π-stacking interactions: δ + δ + face-to-face is repulsive T-shaped stabilizing Slipped-Stack or "Displaced" Stack-stabiliziang Direct ace-to ace stack is favorable only for Arene-Perfluoroarene interaction
on-covalent Interactions 4. Ion-Induced Dipole E = -q 2 α/(4πεε ο ) 2 r 4 δ + δ + δ + δ + δ + δ+ δ + δ δ δ δ δ δ δ Li + α=polarizaility of non-polar molecule note: alkanes are quite polarizable, with many Csp 3 - bonds 5. Dipole-Induced Dipole E = -2µ 1 2 α 2 /(4πεε ο ) 2 r 6 δ + δ δ + δ + δ + δ+ δ + δ+ δ + δ δ δ δ δ δ δ 6. Induced Dipole-Induced Dipole E~1/r 6 London forces, Van der Waals interactions: If there is a large enough surface area for two molecules to interact, these forces can become considerable δ + δ + δ + δ + δ + δ+ δ + δ δ δ δ δ δ boiling point of octane δ =125 C, higher than 2! δ + δ + δ + δ + δ + δ+ δ + δ δ δ δ δ δ δ
on-covalent Interactions Summary: Distance dependence (indicative of strength) of the energy of interaction for various binding forces Monopole Dipole Induced Dipole Monopole 1/r 1/r 2 1/r 4 Dipole 1/r 2 1/r 3 1/r 6 Induced 1/r 4 1/r 6 1/r 6 Dipole
ydrophobic Effect The Association of rganics in Water: "il and water don't mix" Attempt to quantify this tendency: ΔG transfer of a hydrocarbon from the gas phase to water. This number generally scales with the surface area of the hydrocarbon. ydrophobicity Constant π is defined for an R group based on its partitioning in octanol/water: π=log(p/p o ) P o = partitioning of an organic molecule with R between octanol and water P = partitioning ofthe same structure without R between octanol and water ydrophobicity arises from the surface area of the group: R π ΔG(kcal/mol) C 3 0.5 0.68 C 2 C 3 1.0 1.36 C 2 C 2 C 3 1.5 2.05 C(C 3 ) 2 1.3 1.77 C 2 Ph 2.63 3.59 anti gauche Gas Phase anti/gauche: 70/30 water anti/gauche: 55:45 gauche form minimizes surface area
ydrophobic Effect: An Entropy Driven Process Aggregation in water occurs because the exposed hydrocarbon surface area is minimized when two organics come together; aggregation is a spontaneous process in water (ΔG<0) 2 2 2 less surface area exposed to water + ΔG <0 large combined surface area 2 2 2 Cohesive Energy of water- there is a strong penalty for creating a hole in water: break 2 2 interactions, replaced with extremely weak 2 hydrocarbon interactions. Δ (aggregation)~0, so ΔS (aggregation)>0 Water in contact with hydrocarbon becomes more ordered, "ice-like" to compensate for loss of 2 2 interactions. ΔS>0 "ice-like" water has 4-bonds per 2 The release of ice-like water from around the organic molecule on dimerization leads to more normal water, with a concomitant entropy increase less ice-like water
Assessing the Strength of on-covalent Binding The Binding Isotherm Recall that ΔG =-RTlnK, thus a determination of K will give ΔG = ost G=Guest o =[ G] + [] G o =[ G] + [G] [ G] (M) + G G K a = [ G]/[][G] K d = [][G]/[ G] units: M -1 [ G] = [] o K a [G]/1+K a [G] old constant, measure G as a function of free G in solution K a =100M -1 saturation at high concentrations of [G] o, essentially all of [] is converted to [ G] [ G] usually obtained by UV-Vis or MR methods Example: K a =10M -1 K a =1M -1 [G] o /[] o use best fit to the data to obtain K a solve for K a + G G
actors Affecting Acidity Stability of A - A + 2 A - + 3 + 1. Electronegativity / Induction 2. Resonance 5. ybridization > > Cl 3. Bond Strength 2 Te > 2 Se > 2 S > 2 ; I > Br > Cl > 4. Electrostatic Effects + pka=2.31 vs. 3 > > > > Br pka=4.82 6. Solvation 7. Aromaticity 3 C > C 3 C 2 > (C 3 ) 2 C > (C 3 ) 3 C pka=16 8. Cationic Structures B 3 A very B 3 strong acid: pka=17 pka=-7 Ph 3 P + C 3 pka=22.4
pka (C 3 ) 3 C 71 C 3 C 3 50 C 6 12 45 C 2 =C 2 44 C 2 =CC 3 43 PhC 3 41 R 2 38-42 Cycloheptatriene 39 Benzene 37 Ph 2 C 2 33 C 3 SC 3 29 C 3 C 25 C 3 C 2 25 C 3 C 2 C 3 25 acetylene 24 Ph 3 P + -C 3 22 C 3 CC 3 20 PhCC 20 C 3 C 17 Table of pka's pka R 16-18 cyclopentadiene 16 C 3 CC 2 Cl 16 C 3 CC 2 Cl 2 15 RC 2 C 2 C 2 R 13 C 2 (C) 2 11 C 3 2 10 Ph 10 C 3 S 10 (C 3 ) 3 + 10 CC 2 C 2 R 9 + 4 9 C 9 RCC 2 CR 9 2 S 7 imidazole- + 7 Pyridine- + 5 RC 2.21-5.69 2 Se 4 pka 2 Te 3 2 C 2 2 3.63 3.18 2 3.29 3 P 4 2.12 2 CC 2 1.27 Cl 3 CC 2 0.64 3 CC 2 0.52 piciric acid 0.4 C( 2 ) 3 0.14 3-1.44 DMS- + -1.5 3 + -1.74 T- + -2.08 Cl -6.1 Br -8 I -9 2 S 4-9 Cl 4-10
Lewis Acids and Bases ard Bases 2, -, -, RC 2 -, Cl - R, R -, R 2, 3, R 2 2 4 Acids +, Li +, a +, K +, Al 3+, Mg 2+, Ca 2+, B 3, B(R) 3, Al(C 3 ) 3, AlCl 3, RC + Moderate Ph 2, C 5 5, 3 -, Br - Soft R 2 S, RS, RS -, I -, SC -, R 3 P, (R) 3 P, C -, C 2 4, C 6 6, R - e 2+, Co 2+, Cu 2+, Zn 2+, Pb 2+, Sn 2+, B(C 3 ) 3, R 3 C + C 6 5 + Cu +, Ag +, g +, Pd 2+, I 2, Br 2, carbenes, radicals E I =E core + E ES + E overlap electrostatic effects (E ES ) dominate the interaction of hard acids and bases orbital overlap effects (E overlap ) dominate the interaction of soft acids and bases
Additional References ydrogen Bonding 1. JACS, 99, 1316 (1977) 2. Acc. Chem. Res. 20, 39, (1987) 3. J. Chem. Soc., Chem Commun., 1295 (1991) π-effects 1. Chem. Rev., 97, 1303 (1997) 2. Angew. Chem. Int. Ed. 42, 1210 (2003) ydrophobic Effect 1. Angew. Chem. Int. Ed. 32,1545 (1993) 2. Acc. Chem. Res. 23, 23, (1990) Solvent Scales Reichardt, C (1979) Solvent Effects in rganic Chemistry, Verlag Chemie, Weinheim Ion Pairing 1. Szwarc, M. (ed.) (1972) Ions and Ion Pairs in rganic Reactions Wiley, ew York, Vol. 2. 2. Acc. Chem. Res. 2, 87, (1969) Acid Dissociation Constants Acc. Chem. Res. 21, 456, 463 (1988)